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Ecotoxicology and Human Environmental Health
Perfluoroalkyl acids (PFAAs) in serum from 2-4-monthold infants – influence of maternal serum concentrations, gestational age, breastfeeding and contaminated drinking water Irina Gyllenhammar, Jonathan P. Benskin, Oskar Sandblom, Urs Berger, Lutz Ahrens, Sanna Lignell, Karin Wiberg, and Anders Glynn Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.8b00770 • Publication Date (Web): 15 May 2018 Downloaded from http://pubs.acs.org on May 16, 2018
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Perfluoroalkyl acids (PFAAs) in serum from 2-4-month-old infants – influence of
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maternal serum concentrations, gestational age, breastfeeding and contaminated
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drinking water
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Irina Gyllenhammar, † Jonathan P. Benskin,‡ Oskar Sandblom,‡ Urs Berger,§ Lutz Ahrens,#
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Sanna Lignell, † Karin Wiberg,# Anders Glynn¤ †*
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†
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Uppsala, Sweden
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Department of Risk and Benefit Assessment, National Food Agency, P.O. Box 622, 751 26
‡
Department of Environmental Science and Analytical Chemistry (ACES), Stockholm
University, SE-106 91 Stockholm, Sweden Helmholtz Centre for Environmental Research – UFZ, Department Analytical Chemistry,
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§
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Permoserstr. 15, 04318 Leipzig, Germany
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#
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Sciences, Box 7050, 750 07, Uppsala, Sweden
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¤
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Agricultural Sciences, Box 7050, 750 07, Uppsala, Sweden
Department of Aquatic Sciences and Assessment, Swedish University of Agricultural
Department of Biomedical Sciences and Veterinary Public Health, Swedish University of
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*Corresponding author:
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Anders Glynn
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Department of Biomedical Sciences and Veterinary Public Health, Swedish University of
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Agricultural Sciences, Box 7050, 750 07, Uppsala, Sweden
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Telephone: int + 46 18 672091
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E-mail:
[email protected] 24 1
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Abstract
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Little is known about factors influencing infant perfluorinated alkyl acid (PFAA)
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concentrations. Associations between serum PFAA concentrations in 2-4-month-old infants
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(n=101) and determinants were investigated by multiple linear regression and General Linear
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Model (GLM) analysis. In exclusively breastfed infants, maternal serum PFAA
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concentrations 3 weeks after delivery explained 13% (perfluoroundecanoic acid, PFUnDA) to
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73% (perfluorohexane sulfonate, PFHxS) of infant PFAA concentration variation. Median
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infant/maternal ratios decreased with increasing PFAA carbon chain length from 2.8 for
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perfluoroheptanoic acid (PFHpA) and perfluorooctanoic acid (PFOA) to 0.53 for PFUnDA,
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and from 1.2 to 0.69 for PFHxS and perfluorooctane sulfonate (PFOS). Infant PFOA,
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perfluorononanoic acid (PFNA) and PFOS increased 0.7-1.2% per day of gestational age.
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Bottle-fed infants had 2 times lower mean concentrations of PFAAs, and a higher mean
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percentage of branched (%br) PFOS isomers, than exclusively breastfed infants. PFOA,
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PFNA and PFHxS increased 8-11% per week of exclusive breastfeeding. Infants living in an
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area receiving PFAA-contaminated drinking water had 3-fold higher mean perfluorobutane
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sulfonate (PFBS) and PFHxS concentrations, and higher mean %br PFHxS. Pre- and post-
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natal PFAA exposure significantly contribute to infant PFAA serum concentrations,
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depending on PFAA carbon-chain length. Moderately PFBS- and PFHxS-contaminated
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drinking water is an important indirect exposure source.
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2
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TOC Graphic
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Introduction
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Per- and polyfluoroalkyl substances (PFASs) are synthetic fluorinated substances used in
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numerous commercial applications and occurring ubiquitously in humans and the
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environment. Sources of human exposure include food, drinking water, dust, air and the use
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of PFAS-containing consumer products.1-4 Among the ~3000 known PFASs,5 perfluoroalkyl
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acids (PFAAs) are of greatest concern due to their persistence and chain length-dependent
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bioaccumulation potential.6 PFAAs may be formed from degradation of other PFASs
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(commonly referred to as PFAA precursors).7,8
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PFAAs could cross the placenta and are excreted in mother´s milk.9-11 Modeling of
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infant exposure to some PFAAs suggests that in utero exposure and breastfeeding are
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important determinants of blood concentrations.12,13 Food, drinking water, dust and air
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contribute to exposure when the child gets older.4,14-17 High early life exposure to some
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PFAAs is related to lower birth weight and immune toxicity,
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determinants of PFAS concentrations in infant blood is urgently needed for identification of
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infant exposure sources. Moreover, as pointed out by Loccisano et al. 12 more data on PFAA
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concentrations in infants is crucial for development/refinement of infant physiologically-
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based pharmacokinetic (PBPK) models, which are important for risk assessment. To our
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knowledge only one study has reported PFAA concentrations in infants (6 months old),21
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showing higher median concentrations of perfluorohexane sulfonate (PFHxS),
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perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluoronona noic acid
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(PFNA) in infant serum than in cord serum from the same study participants. The increase
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was most likely due to exposure during breastfeeding.21
18-20
and knowledge of
4
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The aim of the present study was to investigate maternal to infant transfer of PFHxS
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(linear and branched isomers), PFOS (linear and branched isomers), perfluoroheptanoic acid
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(PFHpA), PFOA, PFNA, perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid
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(PFUnDA), as well as influence of potential determining factors of infant serum
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concentrations, such as maternal PFAA concentrations close to delivery, duration of in utero
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exposure (days of gestational age at delivery), duration of breastfeeding, infant weight gain,
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and maternal exposure to PFAA-contaminated drinking water.
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Methods
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Study Population
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The study is based on samples and data collected within the POPUP cohort (Persistent
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Organic Pollutants in Uppsala Primiparas), an on-going investigation of POPs in first-time
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mothers and their children that started in 1996.22 The present study is based on recruitment of
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mother/child pairs 1996-1999. From early fall 1996 to May 1999, 395 randomly selected
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primipara women in late pregnancy were asked to participate in the study.23 The Swedish
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speaking women had been recruited in early pregnancy as controls in a case-control study of
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caffeine as a risk factor for miscarriage.24 In total 325 women (82%) agreed to participate in
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the POPUP study.
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The participating women were asked if a maternal blood sample could be taken 3 weeks
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after delivery and an infant sample about 3 months after delivery. The mothers were Swedish-
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born and had singleton births with no birth defects. Almost all women had a full-term
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pregnancy (37–42 weeks), except in a few cases with the shortest gestational age being 35
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weeks and the longest 43 weeks. Women in the POPUP cohort are homogenous regarding
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ethnic background. In 2006, only about 4% of the Swedish population had one or two foreign5
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born parents.25 Maternal sampling 3 weeks after delivery was accepted by 211 participants.
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Infant sampling was accepted by 138 participants. Due to limited blood volumes 101 maternal
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and 107 infant samples were available for PFAA analyses (Table 1). In total 101 matched
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mother/infant samples were available. Informed consent was obtained from all participating
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women. The study was approved by the Ethics Committee of the Medical Faculty at Uppsala
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University (2004:M-177).
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Interviews, Questionnaires and Blood sampling
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In-person interviews, using a structured questionnaire, were conducted at 6-12 and 32-34
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completed gestational weeks.24 Height of the women was measured and women were weighed
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on both interview occasions. Data on maternal characteristics included age, pre-pregnancy
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body mass index (BMI), years of education, place of residence, and smoking habits. At the
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infant sampling, the mothers answered a self-administered questionnaire including questions
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about delivery, and personal characteristics not covered by the interviews, such as data on
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breast-feeding. Vacutainer® or Vacuette® serum tubes were used for blood sampling, and after
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separation serum was stored at -20°C until analysis.
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Chemical Analyses
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The target analytes included C 4 , C6 and C8 perfluoroalkane sulfonic acids (PFSAs; PFBS,
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PFHxS, PFOS) and C 6 -C15 perfluoroalkyl carboxylic acids (PFCAs; PFHxA, PFHpA, PFOA,
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PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFTeDA, PFPeDA; for details see Supporting
118
Information, Table A1). The serum samples were analyzed as described previously.26 In short,
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serum (0.1 g for infants and 0.5 g for adults) was spiked with internal standards (Supporting
120
Information, Table A2) and extracted with acetonitrile (Honeywell CHROMASOLV™,
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≥99.95% purity) in an ultrasonic bath. The concentrated extract underwent dispersive clean-up
6
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with graphitized carbon (Supelclean™ ENVI-Carb™, Sigma-Aldrich). Aqueous ammonium
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acetate (2mM; EMSURE®, Sigma-Aldrich) and volumetric standards (13 C8 -PFOS and 13 C8 -
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PFOA; both from Wellington Labs) were added before instrumental analysis on an Acquity
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ultra performance liquid chromatography system (UPLC) coupled to a Xevo TQ-S tandem
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mass spectrometer (both Waters Corp., Milford, MA, U.S.) operated in negative electrospray
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ionization, multiple reaction monitoring mode. The mobile phase consisted of water and
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acetonitrile (ACN; both containing 2mM ammonium acetate), with the relative proportions
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varied under gradient conditions. ACN-based mobile phases such as that used here are highly
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effective at removing bile acid interferences which may affect PFOS and PFHxS analysis. 27-29
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Further, instrumental parameters are provided in Supporting Information (Table A2).
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Quantification was performed by isotope dilution using a 5-point external calibration curve
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(linear, 1/x weighting), which was run before and after samples. For most targets, analogous
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isotopically labelled internal standards were available. For PFBS, PFTrDA, PFTeDA, and
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PFPeDA, a structurally similar internal standard was used (Supporting Information, Table
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A2). For PFHxS and PFOS, the linear isomer and the sum of all branched isomers (as one
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signal) were quantified separately using a linear isomer calibration curve. For PFOS,
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concentrations obtained from the m/z 499/80 and 499/99 ions were averaged, which provides
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a reasonable estimate of the weight % branched (%br) content in the absence of isomer-
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specific quantification.30 PFHxS was also monitored using m/z 399/80 and 399/99 ions;
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however, since the branched isomer peak in the latter transition was often below method
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detection limits (MDLs), concentrations were only reported from the m/z 399/80 transition.
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Both a procedural blank (0.1 or 0.5 mL Milli-Q water) and QC sample (pooled human
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serum analyzed repeatedly in-house) were included with every batch of samples (see
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Supporting Information, Table A3, for QC performance metrics). In addition, concentrations
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determined in n = 3 replicates of NIST SRM 1957 were compared to reference values to
7
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assess the accuracy of the method (results provided in Supporting Information Tables A4 and
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A5). Measured concentrations in SRM 1957 were consistent with reference values for all
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targets, while coefficients of variation (CVs) in in-house reference serum ranged from 12 -
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36% (median 19%; n = 20; Table A3). For targets observable in method blanks, the MDL was
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based on the mean blank + 3× the standard deviation of the blanks. For those targets with no
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observable blank contamination, detection limits were based on the concentration producing a
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signal-to-noise ratio of 3 in sample chromatograms. Analyses of PFAAs in infants and their
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mothers were accomplished within three different analytical batches in 2013, 2014, and 2016.
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Batch-specific MDLs are provided in Table A6 of the Supporting Information. Further
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method validation parameters are provided in Glynn et al. 2012.26
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Statistical Analyses
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MINITAB 15® Statistical Software for Windows was used for all statistical analyses. When
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PFAA concentrations were below the method detection limit (MDL), MDL/√2 was taken as
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an estimated value in the statistical analyses. The PFAA concentrations in maternal serum
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were measured in different analytical batches and for PFHpA and PFBS the MDL differed
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between the batches (Supporting Information Table A6). In the statistical analysis including
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maternal PFAA data, all PFHpA and PFBS data below MDL in the batch with the highest
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MDL was omitted (batch 3, n=17). The proportions of branched and linear isomers for PFHxS
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and PFOS were expressed as a percentage of the total concentration. Correlations between
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infant and mother serum PFAA concentrations were investigated using the Pearson´s
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correlation test, and only pairs with data >MDL for both the mother and the infant were
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included in the analyses.
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For PFAAs with over 75% of infant data >MDL multiple linear regressions were used
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to analyze if infant serum concentrations are influenced by maternal PFAA concentrations 3
8
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weeks after delivery (ng g-1 ), gestational age at delivery (days), infant weight gain (% of birth
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weight) and duration of breastfeeding (weeks) (Table 1). The inclusion of the potential
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determinants were based on the assumption that they may influence fetal/infant exposure
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(maternal PFAA concentrations, gestational age, duration of breastfeeding) or infant PFAA
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distribution volume (infant weight gain). In univariate analyses infant PFAA concentrations
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did not differ between sexes (Mann-Whitney U test, p>0.05), and infant sex was not included
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as a covariate in the regression models. In this analysis, only data from infants that were
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exclusively breastfed during the whole study period from birth to infant blood sampling were
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included. Stepwise regression analysis was used to estimate how much of the variation in
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PFAA concentrations that could be explained by the variation of each individual determinant
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(partial coefficient of determination, R2 ). Criteria for determinant inclusion in the regression
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model was α50% of concentrations below MDL for PFDoDA, PFTrDA,
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PFTeDA and PFPeDA (Table 2). The observed concentrations differ from those reported for
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6-month-old infants from Germany,21 the only previously published infant study we could
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find in the literature. Different sampling periods (present study:1996-99, German study:2007-
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2009) and ages of the infants (present study:2-4 months, German study: 6 months) are most
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likely important determinants of the observed differences.
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To our knowledge, no other study has reported isomer-specific data on PFHxS and
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PFOS for infants. We found similar %br PFOS and PFHxS in mothers and infants (Table 2),
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suggesting that infant isomer patterns to a large extent are dependent on maternal patterns. In
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Canadian mothers, median %br PFOS (36%) was similar to that of Swedish mothers,
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although Canadian mothers were sampled almost 10 years after the Swedish mothers. 32 In
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maternal serum from China, sampled 2015-2016, branched PFHxS accounted for 14%
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(median) of the total PFHxS and branched PFOS 17% of total PFOS. 33 A comparison of
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maternal %br PFHxS and PFOS between studies is hampered by differences in how branched
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content was determined in each study (e.g. isomer-specific versus sum branched isomer
238
quantification using linear and/or individual branched isomer standards). Nevertheless,
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differences due to ongoing maternal exposure to for instance PFHxS and PFOS precursors in
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China are likely since perfluorooctane sulfonyl fluoride-based chemistry is still used in
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China.33
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Maternal serum/plasma concentrations of PFHxS, PFOS, PFOA, PFNA, PFDA, and
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PFUnDA during pregnancy and a few weeks after delivery both reflect placental and mother´s
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milk PFAA transfer, as shown by strong correlations between PFAA concentrations in
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maternal and cord blood, and between concentrations in maternal blood and mother´s
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milk.9,10,26,34,35 We found positive correlations between maternal and infant PFAA
11
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concentrations, with weakening strength as chain length increased of both long-chain PFCAs
248
and PFSAs (Table 3). This suggests that factors other than maternal concentrations become
249
more important as determinants for infant PFAA concentrations as perfluoroa lkyl chain length
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increases.
251
This is further supported by the decreased strength of association between maternal and
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infant concentrations with increased PFAA carbon chain length among exclusively breastfed
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infants, as determined in multiple log-linear regression analyses (Table 4). Variation in
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maternal PFOA concentrations explained 53% of the infant concentration variation, whereas
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only 13% of the variation in infant PFUnDA was explained by maternal variation. For
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PFHxS, 73% of the infant variation was explained by maternal variation, and the
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corresponding figure for PFOS was 36%. The short-chain PFHpA deviated from this pattern
258
of chain-length dependency, showing a weaker infant/mother correlation than PFOA did
259
(Table 3) and a weaker strength of association (Table 4). For PFAA homologues with less
260
strong infant/mother correlations and associations, contribution of infant exposure sources not
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studied by us may be important, including ingestion of dust, suction on materials containing
262
PFASs, inhalation of fine particles/air, and skin exposure through use of personal care
263
products.4 To what degree these different exposure pathways contribute to total infant
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exposure has not been fully characterized, but the contribution of each component most
265
probably varies with infant age.4
266
Our results suggest that PFAA transfer efficiency from mother to infant decreases with
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increasing perfluoroalkyl chain length, as indicated by the infant/maternal serum
268
concentration ratios (Table 3). On average, PFHpA and PFOA showed higher concentrations
269
in infants than in mothers, PFHxS concentrations were similar, and concentrations for PFNA,
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PFOS, PFDA and PFUnDA were lower in infants. This is in agreement with the previously
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observed chain length-dependent decrease in transfer efficiency over the placenta and from
12
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maternal blood to mother´s milk.9,32,36,37 It has been proposed that decreases in PFAA
273
placental transfer with increased chain length may be due to decreases in water solubility and
274
increases in PFAA affinity to serum albumin.4,37 It has also been hypothesized that there are
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chain length differences in active PFAA transport in the placenta,4,11 although this hypothesis
276
has to our knowledge not been tested. Similarly, it is not known to what degree mammary
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gland active PFAA transport is involved in the carbon chain-dependency of PFAA transfer to
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mother´s milk.
279
In contrast to Fromme et al.21 , our study does not include matched cord blood data. We
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have previously published cord whole blood data for PFOS, PFOA and PFNA in the Uppsala
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study 1996-99.26 Assuming a distribution factor of 2 between serum and whole blood, average
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cord serum concentrations were 2-3 times lower than those in maternal serum sampled in late
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pregnancy,26 which is in accordance with data from Fromme et al. 21 A comparison of
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published cord/maternal serum or plasma PFAA ratios with the infant/maternal serum PFAA
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ratios among Uppsala infants (Table 3) and German infants (plasma) show that the
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infant/maternal ratios generally are higher than the cord/maternal rations.21,32,36 This strongly
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suggests that breastfeeding gives a significant contribution to the PFAA exposure of the
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infants.
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The similar median ratios of infant/maternal linear and branched PFHxS, as well as of
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PFOS isomers (Table 3), show that linear and branched isomers were retained in the infants to
291
a similar degree as in their mothers. A few studies have reported less efficient placental
292
transfer of linear PFOS (relative to branched), but found no isomer specific differences in
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transfer via mother´s milk.10,32,35 To our knowledge, only one study has reported placental
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transfer efficiencies of PFHxS isomers showing, contrary to PFOS, a more efficient transfer
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of the linear isomer than of the branched isomers.33 Our results suggest that the more efficient
296
trans-placental transfer of branched PFOS, and less efficient transfer of branched PFHxS, are
13
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“compensated for” after birth, presumably from mother´s milk, resulting in similar %br
298
isomers in mothers and infants.
299 300
Impact of Duration of Breastfeeding, Gestational Age and Infant Weight Gain
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Concentrations of PFOA, PFNA, PFDA, PFUnDA, PFHxS and PFOS were lower in
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exclusively bottle-fed infants than in exclusively breastfed infants, strongly suggesting that
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mother´s milk is an important source of infant exposure to all these PFAAs (Fig. 1). The
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results are however uncertain since we only had 5 exclusively bottle-fed infants, but the
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importance of breastfeeding as an exposure source of all these PFAAs is supported by our
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findings of lower serum PFAA concentrations also among mixed breast-/bottle-fed infants
307
(Fig. 1). The lower PFAA concentrations in bottle-fed infants are most probably a net result of
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infant excretion and growth dilution of PFAAs accumulated in utero, and much lower PFAA
309
exposures from infant formula than from mother´s milk.38,39 No exclusively bottle-fed infants
310
were living in a district receiving contaminated drinking water, so it was not possible to
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determine the contribution of this potential exposure route.
312
The higher %br PFOS in the few exclusively bottle-fed infants than in exclusively
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breastfed infants (Fig. 1) is most probably a result of the higher placental transfer of branched
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PFOS isomers than of the linear isomer, and a “mother´s milk compensation” with the linear
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isomer among exclusively breastfed infants.10,32,35 Branched PFOS isomers are preferentially
316
excreted in urine in adults compared with the linear isomer, 40,41 but excretion of different
317
PFOS isomers in infants apparently was too slow to cause preferential retention of the linear
318
isomer in bottle-fed infants. The reported lower trans-placental transfer efficiency of branched
319
PFHxS isomers than of the linear isomer33 did not result in lower %br PFHxS concentration
320
in the exclusively bottle-fed infants (Fig. 1). Assuming that the excretion of PFHxS was
14
321
negligible during infancy, the results suggests that the transfer of branched PFHxS isomers to
322
mother´s milk is not higher than transfer of the linear isomer.
323
In the multiple regression analyses of PFAA concentrations in exclusively breastfed
324
infants, duration of breastfeeding explained 90% PFAA-contaminated
384
drinking water between 1996 and 1999, than among infants living in the districts not receiving
385
contaminated water (Fig. 2).
386
Similarly as among Uppsala mothers,31 no influence of contaminated drinking water on
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infant PFOS concentrations was observed (Supporting Information, Table A7), although
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PFOS concentrations in the contaminated drinking water were only slightly lower than those
389
of PFHxS and much higher than PFBS concentrations. Taken together the results suggest that,
390
in contrast to PFBS and PFHxS, maternal PFOS exposure sources other than drinking water
391
were more important indirect determinants of infant PFAA concentrations.
392
%br PFHxS was significantly higher in infants living in Uppsala districts receiving 10-
393
90% and >90% contaminated water than in infants living in the district receiving
394
uncontaminated water (Fig. 2). We have previously proposed that increased %br PFHxS in
395
adult serum, compared to background in a population, may be an indicator for drinking water
17
396
exposure to PFHxS originating from fire-fighting foams.31 Our infant results suggest that
397
enrichment of branched PFHxS persists also in infants of mothers exposed to drinking water
398
PFHxS.
399 400
Strengths and Limitations
401
Our study includes data on PFBS, PFHxA, PFHpA, PFUnDA, PFDoDA, PFTrDA, PFTeDA
402
and PFPeDA which were lacking in Fromme et al. (2011).21 For many of these PFAA,
403
however, concentrations were generally below LOQ, making it impossible to analyze
404
associations with potential determinants. We have data on branched and linear isomers of
405
PFHxS and PFOS in infants, thus enabling a first look at possible isomer-specific differences
406
in mother/infant dynamics of PFHxS and PFOS. We only had PFAA concentration data from
407
5 infants that were exclusively bottle-fed, making the comparisons with PFAA concentrations
408
in exclusively breastfed infants uncertain. However, with supporting data from partially
409
bottle-fed infants we can nevertheless conclude that breast-feeding is a significant source of
410
infant exposure to PFHxS, PFOS, PFOA, PFNA, PFDA and PFUnDA. Moreover our study
411
includes data on several potential determinants not studied before, such as gestational age
412
(duration of in utero exposure), infant body weight gain (growth dilution), and home address
413
in drinking water districts with differences in drinking water PFAA contamination (indirect
414
drinking water exposure). A weakness is that we did not have data on PFAA concentrations in
415
drinking water ingested by the mothers and maternal drinking water consumption, which
416
would have improved the analyses of contribution of maternal PFAA drinking water exposure
417
to infant serum PFAA concentrations.
418
The Swedish infants were only sampled once after birth and more extensive serial
419
sampling of neonates and infants will give better information about factors influencing
420
serum/plasma PFAA concentrations during early childhood. As shown by the decrease in
18
421
strength of determination with increasing PFAA chain length, there are unknown
422
determinants, not studied by us, that have an important influence on infant PFAA
423
concentration.
19
424
Figures
425
PFOA
0.15
0.5
PFHxS
0.10
re as tfe d
20
*
*
0.06 0.04
ng/g serum
15
ng/g serum
2
1
10 5
0.02
%branched PFHxS
re a B
/b re a
st fe d
st fe d
ed B
ot tle -
B
B
re a
st fe d
st fe d /b re a ot tle B
B
ot tle -
B
B
re a
ot tle f
st fe d
st fe d /b re a
ot tle f B
0 ed
0 ed
0.00
ot tle f
ng/g serum
B
PFOS
3
*
0.08
%branched PFOS 60
%branched isomers
10 8 6 4 2
20
B
re a
st fe d
st fe d /b re a ot tle -
re a B
ot tle f B
ot tle B
st fe d
st fe d /b re a
ot tle f B
ed
0 ed
0
*
40
B
%branched isomers
st fe d B
ot tle B
PFUnDA
/b re a
/b re as tfe d
B
re as tfe d
B
ot tle -
B
/b re as tfe d
0.00
ot tle -
0.0
0.05
ot tle fe d
0
ot tle fe d
0.1
ot tle fe d
2
B
ng/g serum
0.2
0.10
re as tfe d
4
0.3
B
ng/g serum
6
*
*
0.4
B
*
8
ng/g serum
PFDA
PFNA
10
426 427
Figure 1. Concentrations (ng g-1 serum) of selected PFAAs in serum from 2-4-month-old infants
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sampled 1996-1999 with different degrees of breastfeeding during the study period. ‘Bottle-fed’ (N=5)
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represents infants which were not breastfed at all prior to sampling. ‘Bottle-/breastfed’ (N=11)
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corresponds to infants that were exclusively breastfed followed by partial/exclusive bottle-feeding
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before sampling. ‘Breastfed’ (N=83) represents infants exclusively breastfed from birth until
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sampling. PFAA concentrations
